Genetics of human lupus nephritis.

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease in which glomerulonephritis represents one of the most severe clinical presentations. Numerous linkage and association studies, as well as the analysis of murine models, have provided ample evidence for a genetic basis for SLE. Genetic susceptibility to SLE results from the combined actions of multiple alleles, each of them conferring a modest incremental risk. SLE susceptibility genes have been identified in 3 major pathways: apoptosis, lymphocyte activation, and clearance of immune complexes and/or apoptotic debris. There also now is evidence that, within SLE patients, renal end-organ targeting also has a genetic basis, which can be divided into 2 branches. There is evidence that susceptibility alleles that are associated with a greater disease severity also are associated with lupus nephritis. There also is evidence for a set of kidney-specific genes that are likely to amplify or to sensitize to the autoimmune pathology.